TY - JOUR
T1 - Severe neurodevelopmental phenotype, diagnostic, and treatment challenges in patients with SECISBP2 deficiency
AU - Stoupa, Athanasia
AU - Franca, Monica Malheiros
AU - Abdulhadi-Atwan, Maha
AU - Fujisawa, Haruki
AU - Korwutthikulrangsri, Manassawee
AU - Marchand, Isis
AU - Polak, Gabrielle
AU - Beltrand, Jacques
AU - Polak, Michel
AU - Kariyawasam, Dulanjalee
AU - Liao, Xiao Hui
AU - Raimondi, Chantalle
AU - Steigerwald, Connolly
AU - Abreu, Nicolas J.
AU - Bauer, Andrew J.
AU - Carré, Aurore
AU - Taneja, Charit
AU - Mekhoubad, Allison Bauman
AU - Dumitrescu, Alexandra M.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/12
Y1 - 2024/12
N2 - Purpose: Defects in the gene encoding selenocysteine insertion sequence binding protein 2, SECISBP2, result in global impaired selenoprotein synthesis manifesting a complex syndrome with characteristic serum thyroid function tests due to impaired thyroid hormone metabolism. Knowledge about this multisystemic defect remains limited. Methods: Genetic and laboratory investigations were performed in affected members from 6 families presenting with short stature and failure to thrive. Results: Four probands presented a complex neurodevelopmental profile, including absent speech, autistic features, and seizures. Pediatric neurological evaluation prompted genetic investigations leading to the identification of SECISBP2 variants before knowing the characteristic thyroid tests in 2 cases. Thyroid hormone treatment improved motor development, whereas speech and intellectual impairments persisted. This defect poses great diagnostic and treatment challenges for clinicians, as illustrated by a case that escaped detection for 20 years because SECISBP2 was not included in the neurodevelopmental genetic panel, and his complex thyroid status prompted antithyroid treatment instead. Conclusion: This syndrome uncovers the role of selenoproteins in humans. The severe neurodevelopmental disabilities manifested in 4 patients with SECISBP2 deficiency highlight an additional phenotype in this multisystem disorder. Early diagnosis and treatment are required, and long-term evaluation will determine the full spectrum of manifestations and the impact of therapy.
AB - Purpose: Defects in the gene encoding selenocysteine insertion sequence binding protein 2, SECISBP2, result in global impaired selenoprotein synthesis manifesting a complex syndrome with characteristic serum thyroid function tests due to impaired thyroid hormone metabolism. Knowledge about this multisystemic defect remains limited. Methods: Genetic and laboratory investigations were performed in affected members from 6 families presenting with short stature and failure to thrive. Results: Four probands presented a complex neurodevelopmental profile, including absent speech, autistic features, and seizures. Pediatric neurological evaluation prompted genetic investigations leading to the identification of SECISBP2 variants before knowing the characteristic thyroid tests in 2 cases. Thyroid hormone treatment improved motor development, whereas speech and intellectual impairments persisted. This defect poses great diagnostic and treatment challenges for clinicians, as illustrated by a case that escaped detection for 20 years because SECISBP2 was not included in the neurodevelopmental genetic panel, and his complex thyroid status prompted antithyroid treatment instead. Conclusion: This syndrome uncovers the role of selenoproteins in humans. The severe neurodevelopmental disabilities manifested in 4 patients with SECISBP2 deficiency highlight an additional phenotype in this multisystem disorder. Early diagnosis and treatment are required, and long-term evaluation will determine the full spectrum of manifestations and the impact of therapy.
KW - Neurodevelopmental disorder
KW - SECISBP2
KW - Selenoprotein
KW - Short stature
KW - Thyroid hormone metabolism defect
UR - http://www.scopus.com/inward/record.url?scp=85207639558&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85207639558&partnerID=8YFLogxK
U2 - 10.1016/j.gim.2024.101280
DO - 10.1016/j.gim.2024.101280
M3 - Article
C2 - 39315526
AN - SCOPUS:85207639558
SN - 1098-3600
VL - 26
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 12
M1 - 101280
ER -